Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis

Background: This meta-analysis assessed the predictive and prognostic value of tumor infiltrating lymphocytes (TILs) in neoadjuvant chemotherapy (NACT) treated breast cancer and an optimal threshold for predicting pathologic complete response (pCR).Methods: A systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible studies published before April 2022. Either a fixed or random effects model was applied to estimate the pooled hazard ratio (HR) and odds ratio (OR) for prognosis and predictive values of TILs in breast cancer patients treated with NACT. The study is registered with PROSPERO (CRD42020221521).Results: A total of 29 published studies were eligible. Increased levels of TILs predicted response to NACT in HER2 positive breast cancer (OR = 2.54 95%CI, 1.50-4.29) and triple negative breast cancer (TNBC) (OR = 3.67, 95% CI, 1.93-6.97), but not for hormone receptor (HR) positive breast cancer (OR = 1.68, 95 %CI, 0.67-4.25). A threshold of 20% of H & E-stained TILs was associated with prediction of pCR in both HER2 positive breast cancer (P = 0.035) and TNBC (P = 0.001). Moreover, increased levels of TILs (either iTILs or sTILs) were associated with survival benefit in HER2-positive breast cancer and TNBC. However, an increased level of TILs was not a prognostic factor for survival in HR positive breast cancer (pooled HR = 0.64, 95%CI: 0.03-14.1, P = 0.78).Conclusions: Increased levels of TILs were associated with increased rates of response to NACT and improved prognosis for the molecular subtypes of TNBC and HER2-positive breast cancer, but not for patients with HR positive breast cancer. A threshold of 20% TILs was the most powerful outcome prognosticator of pCR.